Project Summary/Abstract Advances in the global fight against HIV/AIDS have enabled more women living with HIV to access antiretroviral (ARV) treatment prior to conception, during pregnancy and throughout breastfeeding, resulting in dramatic reductions in perinatal and breastfeeding transmission of HIV. While appropriate focus has been placed on the care and survival of the declining population of HIV-infected children, with ~ 150,000 perinatal HIV infections occurring in 2015, an urgent public health need exists to understand why the over one million HIV-exposed uninfected (HEU) infants born each year, the much celebrated ?AIDS free generation?, are failing to achieve comparable health and developmental outcomes compared with children born to HIV- uninfected women. Understanding the biological and structural mechanisms underlying these disparities has been hindered by i) inconsistencies in definitions for key HEU child exposures and outcomes used across studies with heterogenous methodologies; and ii) identification of concerning signals often without an appropriate HIV-unexposed comparator group and/or inadequate power to exclude confounding. Therefore, we are proposing a data harmonization project entitled ?INFORM ? AIDS FREE: A Harmonized INfrastructure FOR Monitoring Global Health Outcomes of the AIDS FREE? Generation?. Adapting successful approaches used by existing global HIV-related data harmonization projects, we will establish a harmonized data infrastructure employable in clinical settings and research studies to rigorously compare HEU and HIV- unexposed child outcomes and drivers of these outcomes. We hypothesize that a harmonized infrastructure for capturing standardized variables pertinent to HEU child outcomes can be developed and feasibly implemented in selected high burden HIV countries, resulting in pooled data needed to inform interventions and improve outcomes. Our two-year project plan will be guided by the following specific aims: Specific Aim #1: Through expert panel consensus and technical working groups, establish HEU child outcome domains and develop case definitions around specific priority exposures and outcomes. Specific Aim #2: Create data tables and online tools to facilitate data collection at health facilities. Specific Aim #3: Pilot data-capture methods focused on HEU infectious morbidity and mortality in South Africa and Botswana, two settings with large HEU child populations, with support from national and local government health personnel. This epidemiologically rigorous proposal will lay the foundation for pooling HEU child health outcomes data from routine child health programs and research cohorts. We will collaborate with national, local, and parastatal public health bodies to ensure that project data informs HEU health policies. It is provides an organized approach to elucidate the biological and structural mechanistic drivers underlying HEU child health, developmental, and survival disparities, the first step to ensure that the ?AIDS Free Generation? can thrive.